not rcs,~nllll~ a cigarette (slwh as many large cigars do not) and has a . tlistillctivp cigar taste and aroma IS of consulerahle srgmficance in rrrakinp this determination" (202). Cigars arc also classified by size. "Small cigars'! weigh not more than 2 ponnds pw thousand and Y nrpe cigars" weigh more than 2 pom~ds per thousand. "Large cigars" are further divided into seven classes for tax purposes based on the retail price intended by the manufacturer for such cigars (96). Cigars are made of filler, binder. and -x-rapper tobaccos. Most cigar tobaccos are air-cured and then fermented. More recently, reconsti. tuted cigar tobaccos have been used as wrapper. binder. or both. Cigars are either hand-rolled or machine made. Some brands of small cigars are manufactured on regular cigarette making machines. The aging 2nd fermentation processes xed in cigar tobacco production producp chemical catalytic, enzymatic. or bacterial transformations as eri- den& by increased tempcmtnrc. oxygen utilization, and carbon dioxide generation within fermenting cigar tobaccos. In this comples process. up to 20 percent of xhe dry weight of the leaf is lost through decreases in the concentration of the most readily fermentable ma- terials such as carbohydrates, proteins, ~1~1 alkaloids. The flavor and aroma of cigar tobaccos are in large measure the results of precisely controlled treatment during the fermentation process (35.36,112). P'ipe Tobnccos The definition of pipe tobacco used by the 1'S Government was repealed in 1966 and therr is no Federal tax on pipe tobaccos. The most popular pipe tobaccos are made of Burley : however. many pipe tobaccos are blends of different types of tobacco. A fen- contain a significant proportion of midrib parts that arc crrrshed between rollers. "S aucing" material. or casings containing licorice. sweetening agents. slyars. and other flavorinK nntrrinls are added to improve the flavor. aroma. and s~nolcc taste. These ndtlitives modifyv the characteristics of smoke components (112). Because of the nniqur curing and processing methods used in the production of cigar and pipe tobaccos. significant physical and chrmi- cal differences esist betn-cm pipe and cigar tobaccos and those used iI1 176 cigarettes. The extent to which these changes may alter the health ronsequcnces of smoking pipes and cigars can best be estimated by an analysis of the potentially harmful chemical constitutents found in tile smoke of these tobaccos. the tumorigenic activity of smoke conden- sates in experimental animals, and a review of the epidemiological data which has acclm~ulatcd on the health etfects of pipe and cigar smoking. Chemical Analysis of Cigar Smoke Only a few studies have been conducted that compare the chemical constituents of cigar smoke with those found in cigarette smoke. Hoffmann, et al. (&I) compared the yields of several chemical com- ponents in the smoke from a plain 85 mm. cigarette, two types of cigars, and a pipe. The particulate matter. nicotine. benzo( a) pyrene! and phenols were determined quantitatirely in the smoke of these tobacco products. One cigar tested was a 135-mm.-long, 7.8-g.> U.S.- made cigar. The other was a handmade TIavana cigar 147 mm. long aeighing 8.6 g. The relative content of nicotine in the particulate matter produced b;v the cigars was similar to that of the cigarette tars. The benzo(a)pyrene and phenol concentrations in the cigar rondensate was two to three times greater than in cigarette "tar" (t,able 4). Kuhn (58) compared the alkaloid and phenol content in conden- sates from an BO-mm. Bright-blend cigarette sold commercially in hustria with that obtained' from 103-mm. cigars. These were tested TABLE 4.--,qmou,nts ?f set'erar! components qf 1 g. ?f particulate material from mainstream smoke of tobacco products Compound U.S. IIavans cigar A cigar II (b) (b) Stsndatd Piw tobacco in pipe (h) 65 mm. 85 mm. Cigarette plain U.S. plaiu U.S. tobacco cigarette cigarette in pipe (8) (h) Nicotine (mg.) _ _ _ - - . _ _ _. 46. 2 63. 6 56. 1 61. 0 65. 9 77. 4 Benzo(a)pyrene (pg.) - - _ - 3. 9 3. 6 6. 0 3. 6 1. 2 1. 3 Phenol (mg.) ____ --- _____ 8. 2 6. 7 15. 0 7. 3 2. 9 4. 1 O-Cresol (mg.) _ _ _ _ _ _ - _ _ - 1. 6 1. 7 1. 9 1.4 .6 .8 mtp-Cresol (mg.).-----. 4. 8 3. 8 5. 6 3. 4 1. 4 1. 9 mtp-Ethylphenol (mg.)-- 1. 1 1. 5 1. 1 1.3 .7 .7 ' smoking condition%: b) 1 puff pw minut?, duration 2 SK., puff rolume 35 ml. (b) 2 puffs prr minute, duration 2 sec., puff volume 35 ml. Smw: IIoffnlaIm, et al. ($5). 177 wit11 and without the USC of a cellulose acetate filter. The concentr,. tions of total alkaloids and phenol in the cigar smoke condensate tverp essentially the same as in the cigarette condensate: bnt pyridine valu& were about 2?,/2 times higher in the cigar condensate. Campbell and Lindsey (17) measured the polycyclic hydrocarbon levels in the. smoke of a small popnlnr-type cigar 8.8 cm. long, weighi% 1.9 g. Significant, quantities of ant.hracene, pyrene, fluoranthene, and benzo (a) pprene were detected in the unsmoked cigar tobacco, in con. centrat.ions much greater than those found in Virginia cigarettes but of the same order as those folmd in some pipe tobaccos. The smoking process contribntcd considerably to t,he hydrocarbon content of the smoke. Table 5 compares the concentrations in the mainstream sm& of cigarettes, cigars, and pipes of four hydrocarbons frequently found in condensates. The authors reported that the mainstream smoke from a popular brand of small cigar contained the pol.ycyclic aromat.ic hydrocarbons : acenapht.h;v-lene, phenanthrene, anthracene, pyrene, ilnoranthene, and benzo(a) pyrene. The concentrations of these hydr". carbons in the mainstream smoke mere greater than those found in Virginia cigarette smoke.. Osman, et al. (69) analyzed the rolat,ile phenol conte.nt of cibr smoke collectcld from a 7-g. American-made cigar with domestic filler, After quantitative analysis of phenol. cresols? xylenols, and met.a and para ethyl phenol, the, ant,hors concluded that the levels of these corn.. pounds were generally similar to those reported for cigarette smoke. Osman and Barson (68) also analyzed cigar smoke for benzene, tolnene. ethyl benzene, m-, p-, and o-xylene, m- and p-ethyltoluene, 1,"+trimethylbcnzene, and dipentene, and generally found levels wit,hin the range of those previously reported for cigarette condensates. In summary, available evidence suggests that cigar smoke contains many of the same chemical Sconstit.urnts, including nicotine and other alkaloids. phenols, and polycyclic aromatic. hydrocarbons as are found TABLE 5.-L4 comparison qf seaerai chemical compounds found in thf mainstream smoke qf cigars, pipes, and cigarettes 1 This is a liglu pipe toharco. Sourre: Camph4, J. 11.. Lindsey, A. J. ($7). 178 in cigarette smoke. Most of these compounds are found in concentra- tions which equal or exceed levels found in cigarette "tar." A more complete pict,ure of the carcinogenic potential of c.igar "tars" is ob- tained from experimental data in animals. Mortality Overall Mortality Several large prospective studies have examined the health conse- quences of various forms of smoking. The results of these investiga- tions have been reviewed in previous reports of the Surgeon General in which the major emphasis has been on c.igarette smoking and its efl'ect on overall and specific mortality and morbidity. The following pages present a current review of the health consequences of smoking pipes and cigars. Data from the prospective investigations of Dunn, et al. (31), Rue& et al. (16), Hirayama (Q), and Weir and Dunn (105) are not cite.d, because in these studies a separate category for pipe and cigar smokers was not established. The smoking habits and mortality experience of 187,783 white men between t.he ages of 50 and 69 who were followed for 44 months were reported by Hammond and Horn (41). The overall mortalit,y rates of men who smoked pipes or cigars were slightly higher than the rates of men who never smoked. The overall mortality rate of cigar smokers was slight.ly higher than that of pipe smokers. In a study of 41,000 British physicians, Doll and Hill (%`, 27) re- ported the overall mortality of pipe and cigar smokers as being only 1 percent greater than that among nonsmokers. Be& (9)) in a study of 78,000 Canadian vet~erans, reported overall mortality rates of pipe and cigar smokers slightly above those of nonsmokers. Kahn (50) exam- ined the death rates and smoking habits of more than 293,000 U.S. veterans and Hammond (38) examined the smoking habits of and mortality E&S experienced by 440,559 men. In these studies, pipe smokers experienced mortality rates similar to those of men who never smoked regularly, whereas cigar smokers had death rates somewhat higher than men who never smoked regularly. Table 6 summarizes the results of these five studies. Thus, data from the major prospective epidemiological studies demonstrate that the use of pipes and cigars results in a small but defi- nita increase in overall mortality. Cigar smokers have somewhat higher death rates than pipe smokers, and mixed smokers who use cigarettes in addition to pipes and cigars appear to experience an inter- mediate level of mortality that approaches the mortality experience of cigarette smokers. 495-028 -73-13 179 TABLE 6.--Mortality ratios for total deaths by type of smoking (1~~~ 0 nW Smoking type Author, reference NiXI- Cigar Pipe Cigar Cigarette Ciparette Mixed - smoker only Only snd pipe and cigar and pipe (cigarette %amtts and other) 0llly Hammond and Horn 1 (40)--- 1. 00 1. 22 1. 12 1. 10 1. 36 1. 50 1. 43 1. 68 Doll and Hill (d6)-v----- 1.00 --_- --_- 1.01 -_-___ -______ 1. 11 1. 28 Best (9).------ 1.00 1. 06 1. 05 98 Kahn (&I---__ 1. 00 1. 10 1. 07 1108 1. 22 1. 26 1. 13 1. 54 -_--__ -- _____ 1. 51 1. 84 Hammond 4 (38)-------_- 1.00 1.25 1.19 1.01 ______ _______ 1. 57 1. 86 ~- 1 Only mortality ratios for ages 50 to 69 rue pwrented. 1 Only mortality ratios for ages 55 to 64 BE prerented. Aforta7ity and Dose-Response Relationships A consistent association exists between overall mortality and the total dose of smoke a cigarette smoker receives. The methods most frequently used to measure dosage of tobacco products are: Amount smoked, degree of inhalation, duration of smoking experience, a@ at initiation, and the amount of tar in a given tobacco product. For cigarette smokers, the higher the dose as measured by any of these parameters, the greater the mortality. The significance of the small increase in overall mortality t,ha.t occurs for the entire group of pipe and cigar smokers can be anal;yzed by examining the mortality of subgroups defined by similar measures of dosage as used in the study of cigarette smokers. AMOUNT SMOKED Hammond and Horn (&I) reported an increase in the overall mor- ta.lity of pipe and cigar smokers with an increase in the amount smoked. Individuals who smoked more than four cigars a day or more th,an 10 pipefuls a day had death rates significantly higher than men who ne.ver smoked (PCO.05 for cigar smokers and PCO.05 for pipe smokers) (table `7). Cigar and pipe users who smoked less than this amount experienced an overall mortality similar to men who never 180 smoked. The study of Canadian veterans (.9) also contained evidence of a dose-response in mortality bg anlonnt smoked for cigar smokers. No dose.-response relationship was observed among pipe smokers (table 8). Kahn (50) reported a consistent, increase in overall morta.lity wit,11 an increase in the amount smoked for both pipe and cigar smokers (table 9). Hammond (38) f ound no consistent relationship between overall mortality and t.he number of cigars or pipefuls smoked (table 10). TABLE T.-Mortality ratios for total deaths of cigar and pipe smokers by amount smoked-Hammond and Horn Amount smoked - Number of deaths Observed Expected Mortality ratio Nonsmoker_.___.___-.__________________ 1, 664 1, 664 1. 00 Cigar only : Total..._- ._____ - __.___.____ _--_---_ 653 598 1. 09 1 to 4 cigars ____ -_- ___________ -_---- 410 400 1. 03 >4 cigars---~--- .___._.___ -__-_---- 229 185 1. 24 Pipe only: Total ________._ - _____ -.--_-_-__-__- 609 560 1. 09 1 to lOpipefuls__-_-___-__----------- 391 374 1. 05 > 10 pipefuls ____ _ -. _ _ _. _. . . ____ _ _ _ _ _ 204 172 1. 19 Source: Hammond, E. C., Horn, D. (40). TABLE 8.-Mortality ratios for total deaths of cigar and pipe smokers by amount smoked--Best Amount smoked Number of deaths __-- Observed Expected Mortality ratio Nonsmoker- _ _ _ _ _ _ _ _ . _ - _ _ - _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ Cigar only : 1. 00 Total----- ____ -_-___--_- _______ 1 to2cigars--- ________________ - 3 to 10 cigars- __.___ -___ ________ >10 cigars _____________________ Pipe only: 90 82. 07 1. 10 64 56.05 1. 14 23 19. 40 1. 19 1 1. 59 .63 Total ____ -__-_-_-___--_---_-___ 570 566. 99 1. 00 1 to 10 pipefuls ______ -_-_- _______ 374 370. 09 1. 01 10 t,o 20 pipefuls- - _ _ _ _ _ _ - __ __ _ _ _ 141 140.84 1. 00 > 20 pipefuls- _ _ _ _ _ _ _ _ _ _ _ _ _ _ - _ _ _ 36 35.90 1. 00 Source: Best, E. W. R. (9). The above evidence suggests that a dose-response relationship may exist between t.he number of cigars and pipefuls smoked and overall mortality. However, because of the high-mortality rate of ex-smokers of cigars and pipes, it is difficult to interpret the data presented wit,h- out including this group with the continuing smokers. Without data which examines patterns of both daily rate of smoking and inhalation at various age levels, no firm conclusions can be drawn `as to the nature of this dosage relationship. TABLE 9.-Mortality ratios j'or total deaths of cigar and pipe smokers by age and amount smoked-Kahn - Amount smoked Mortality ratio, age 56 to 6-i 65 to 74 Nonsmoker_-_---___--________.__ _______ - _______ Cigar only : Total-_--__--____-_.____-_______________~-- lto4cigarsperday _._____._______ - _____ -___ 5toScigsrsperday---- ___. ---__--__- _____ -- >Scigarsperday--- .___ - _._______ - _____ -___ Pipe only: Total ______ --___---__---___-- ____ -___- _____ 1 to 4 pipefuls per day----_.-- _____ - _____ -___ 5 to 19 pipefuls per day- _ - _. ____ ____ __-_ _- __ _ >19 pipefuls per day_---__.---___--_________ 1. 00 1. 01 1. 08 89 1: 14 1. 00 1. 23 1. 65 1. 28 1. 08 1. 16 1. 04 1. 00 1. 06 91 1: 10 1. 18 Source: Kahn, H. A. (50). TABLE lo.-Mortality ratios -for total deaths of cigar and pipe smokers by amount smoked-Hammond Amount smoked MO&t/p Amount smoked Mortality rat10 Nonsmoker--- .___ -.._-- ___. 1. 00 Current pipe smokers: Current cigar smokers: Total- _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ . _ 1. 04 Total_--_._---___-------- 1. 09 1 to 9 pipefuls per day- _ _ _. 1. 08 1 to 4 cigars per day--._--- 1. 03 >9 pipefuls per day---_-_- .92 >4 cigars per day--------- 1. 18 Source: Hammond. E. C. (93). 182 Inhalation of tobacco smoke directly exposes the bronchi and the lungs to smoke and results in the absorption of the. soluble constituents of the gas and particulate phases. Without inhalation tobacco smoke only reaches the oral cavity and the upper digestive and respiratory tracts and does not reach the lungs where further direct effects and systemic absorption of various chemical compounds can m.ur. Although the smoker has some voluntary control over the inhalation of smoke, the physical and chemical properties of tobacco smoke to a degree determine its acceptability and "inhalability.!' The condensate of pipe and cigar smoke is generally found to be alkaline when the pH is measured by suspending a. Cambridge filter in CO,-free water. Cigarette condensate is slightly acidic as measured by this method. Since alkaline smoke is more irritating to the respira- tory tract? it has been assumed that, the more alkaline smoke of pipes and cigars mas in part responsible for the lower levels of inhalation reported by pipe and cigar smokers. Brunnemann and Hoffmann (15) have analyzed the pH of whole, mainstream smoke of cigar&es and cigars on a puff-by-puff basis using a pH electrode suspended in main- stream smoke. Smoke from several U.S. brands of cigaret,tes was found to be acidic throughout the entire length of the cigarette. Of interest was the finding that cigar smoke also had an acidic pH for the first tao-thirds of t.he cigar and became alkaline only in the last 20 to 40 percent of the puffs from t.he cigar. Available epidemiological evidence indicates that most cigar smokers do not inhale the smoke and most cigarette smokers do. The fact that smoke from the first. half or more of a cigar is acidic, near the range of pH values commonly found in cigarette smoke, and becomes alkaline only toward the end of the cigar might suggest that the pH of the smoke of a tobacco product may not be the only factor that influences inhalation patterns. Per- haps "tar" and nicot.ine levels as well as the concentration of ot,her "irritating'? chemicals also affect the degree to which a tobacco smoke Rill be inhaled. Nicotine is rapidly absorbed into the blood stream from the lungs when tobacco smoke is inhaled. The amount of nicotine absorbed from the lungs is primarily a function of the nicot.ine concentrat.ion in the smoke and the depth of inhalation. Some nicotine may also be ab- wrbed t.hrough the mucous membranes of the mouth. This is more likely to occur under alkaline conditions when nicotine is unprot,onated (3, 15, 79). Th' 1s suggests that cigar smokers may be able to absorb SOme nicotine through the oral cavity without having to inhale, par- ticularly during the time that the smoke from the cigar is alkaline. \{Tith the development, of sensitive measures of serum nicotine levels (~8) the extent, to which nicotine is absorbed through the membranes of the mouth in pipe and cigar smokers can be more accurately determined. Inhalation patterns of smokers were determined in several of the large prospective and some of the retrospective epidemiologioa.1 studies. Inhalation was usually determined by the administration of a que. tionnaire that required a subjective evaluation of one's own patterns of inhalat.ion. Although the accuracy of t.hese questionnaires has not been confirmed by an objective measure of inhalation, such as carbosS. hemoglobin or serum nicotine levels, their reliability is supported by mortality data, whi& demonstrate higher overall and specific death rates with self-reported increases in the depth of inhalation. Doll and Hill (26) and Hammond (38) presented information on inhalation patterns of pipe, cigar? and cigarette smokers (figs. 1,2,3! and t,able 12). Some 80 to 90 percent, of cigarette smokers reported inhaling, with the majority of individuals inhaling moderately cr deeply, whereas most pipe and cigar smokers denied inhaling at all. Pipe smokers reported slightly more inhalation than cigar smokem For each type of smoking, less inhalation was reported by older smokers. This change may represent less awareness of inhalation, differences in smoking habits of successive cohorts of smokers, or it may reflect t,he operation of selective factors which favor survival of noninhalers. The Tobacco Research Council of the TTnited Kingdom has, since 1957, periodically reported the use of tobacco products by the British. Figure 1 .-Inhalation among pipe smokers by age. No inhalation Some inhalation 34.8 31.2 26.2 23.9 25.5 I 1 Age 40 50 60 70 80 SOURCE: Hammond, E. C. (38). 184 Figure 2.- Inhalation among cigar smokers by age-Hammond. No inhalation Some inhalation 26.4 22.9 17.1 13.7 18.5 Age 40 50 60 70 80 SOURCE: Hammond, E. C. (38). Figure 3 .-Depth of inhalation among cigarette smokers by age.-Hammond, Slight inhalatir .._. --3n Moderate inhalation DeeP inhalation None I J Age 40 50 60 70 80 SOURCE: Hammond, E. C. (38). Recent reports edited by Todd have contained data on the inhalation pattern of cigar, pipe, and cigarette smokers (92, 93, 94). Table 11 shows that most, cigarette smokers inhale a "lot" of "fair amount" lrhereas most pipe and cigar smokers do not inhale at all or "just a little.`Y Little change is observed in t,he inhalation patterns of a given product since 1968. Best (9) reported inhalation data among male cigarette smokers by smoking intensity and age group, but, did not report, the inhalation s 185 patterns of pipe and cigar smokers. The overall mortality rates of current pipe smokers who inhaled at, least slightly were reported by Hammond (38) as being somewhat higher than for men who never smoked regularly. The overall mortality rates of current cigar smokers who reported inhaling at least slightly were a.ppreciably higher than for men who never smoked regularly (table 13). ,4vailable evidence indicates that cigarette smokers inhale smoke to a greater degree than smokers of cigars or pipes. Once a smoker has learned to inhale cigarettes, hovvever, there appears to be a tendency to also inhale the smoke of other tobacco products. For cigars, this is evident.ly true whether one smokes both cigarettes and cigars or switches from cigarettes to cigars (tables 14,X, 16). Bross and Tidings (14) examined the inhalation patterns of smokers of large cigars, cigarettes, and those who switched from one tobacco product to another (table 15). Nearly 75 percent of those who Kere currently smoking only cigarettes reported inhaling "almost every puff" and only 7 percent never inhaled. The opposite was true for per- sons who had always smoked only cigars among whom 4 percent re- TABLE 11 .-The extent of inhaling pipes, cigars, and cigarettes by British males aged 16 and over in 1968 and 1971 Amount of inhalation - Tobacco product Cigars Pip3 Cigarrttes ----__ 1963 1971 1968 1971 19% 1971 Inhale a lot-. .________________ .____ 23 19 8 8 47 47 Inhale a fair amount----------- _____ 16 19 10 8 31 30 Inhale just a little _____________ .____ 27 27 24 26 13 15 Do not inhale at all- ____. - _____ ._--_ 34 35 59 58 9 6 Total------- ______ -- ___. .____ 100 100 100 100 100 100 Source: Todd, 0. F. (93, 94) TABLE 12.--Inhalation among cigar, pipe, and cigarette smokers by age--DoU and Hill Smoking type Percentage of inhalers, age .25 to 34 35 to 44 45 to 54 55 to 64 wit074 >i4 Cigar and pipe-- ___._. --___--- 12. 00 10. 00 7. 00 5. 00 4. 00 4. 00 Mixed (cigarette and other)_-- _ - 74. 00 60. 00 47. 00 36. 00 30. 00 26. 00 Cigarette only-----.----___-_- 90. 00 85. 00 75. 00 66. 00 58. 00 41.00 Source: Doll, R., Hill, A. B. (?6) 186 ported inhaling almost every puff a.nd 89 percent said they never inhaled. Cigar smokers who also smoked cigarettes reported inter- mediate levels of inhalation between the cigar only and cigarette only categories. Inhalation patterns were similar whether the individual continued to smoke both products, stopped smoking cigarett,es but continued smoking cigars, or stopped smoking cigaret,tes and s\v-itche,d to cigars. In all three groups. about 20 percent reported inhaling "almost every puff." This suggests that once an individual's inhalation patterns are established on cigarettes, he may be more likely to inhale cigar smoke if he switches to cigars, or uses both cigars and cigarettes, than the cigar smoker who has not smoked cigarettes. Todd (93) reported similar data for a sample of smokers in the ITnited Kingdom (table 16). The prevalence of inhaling a "lot!' or `(fair amount" of smoke was highest among cigarette smokers who were currently smoking cigarettes (77 percent) and lowest among current cigar smokers who had previously smoked only cigars or pipes (18 percent). Individuals who switched from cigarettes to cigars main- TABLE 13.--Mortality ratios -for total deaths of cigar and pipe smokers by age and inhalation-Hammond Inhalation Mortality ratio. age 45 to 64 6.5 to 84 Nonsmoker___-_____-_____-__-______________________ 1. 00 1. 00 Cigar only : Total__-_____-__-__-____________________------~ 1. 09 . 98 Noinhalation-_-- _____ - _____ - ___.___.___________ 1. 02 91 Some inhalation ___F_.______ -__-___-_-___-___-__- 1. 28 1: 37 Pipe only: Totsl_-_--_____-________________________------- 1. 04 . 95 No inhalation-_- ____________ - _____ - _.___________ 98 87 Some inhalation ___________ --__--__-___- _____ -___ 1. 21 1: 11 Source: Hammond, E. C. ($8) TABLE IJ.--Percentage of British male cigar smokers who reported inhaling a lot or a fair am0un.t by type of product smoked Type of product 1968 1971 Number of Percent Number of Percent individuals individuals Cigars only- __ _ __ __ _ _ _ __ _ ___. __ _ _ _ _ _ C' lgars and cigarettes-._-. . _ . ~. - - ~. . - cigars and pipes.__ _ _ _ _ - _ - - _ _ . _. _. _ . _ Cigars, cigarettes, and pipes- _ _ _ - -. - - - 706 23. 0 111 27. 0 1, 193 42. 0 277 44. 0 596 35. 0 109 32. 0 26 52. 0 15 32. 0 Source: Todd, C. F. (93, 91). 187 tained somewhat higher levels of cigar smoke inhalation than those cigar smokers who had never smoked cigarettes (30 percent). Todd (93) examined further the relationship between the inhalation of cigarette and cigar smoke. In general, cigarette smokers who switched to cigars mere much less likely to report inhaling cigar smoke than cigarette smoke ; how-ever, those who in the past reported inhaling cigarette smoke a "lot" or "fair amount" were much more likely to report inhaling cigar smoke to the same degree than those ex- cigarette smokers who in the past did not inhale the smoke of their cigarettes (table 17). TABLE IS.-Percentage of inAn%u& reporting inhalation of "almost every puf of tobacco smoke by current and previous tobacco usage and type of tobacco used Type of tobacco smoked Number PBICBll- "Opd&C - __ of Type inhaled Current usage Previous lEa@ p.3tiMltS %r inh ed Lower Upper Cigarettes only ____ Cigarettes on1.y ____ 2, 359 Cigarette--- 74. 8 73. 1 76. 6 Cigars only- _ -__-_ Cigars only- - ---- - 649 Cigars----- 4.5 3. 0 6. 0 Cigarettes and Cigarettes and 520 -----do _____ 20.4 10.5 28.6 cigars. cigars. Cigan- _ _ _ _ - - _ _ _ _ Cigarettes and 93 _____ do _____ 18. 3 9. 0 30. 0 cigars. None ______ -----_ Cigarettes and 186 -----do _____ 21.5 17.8 24.2 cigars. Cigars- _ _ _ - - - - _ _ _ Cigarettes only -.-- 64 _----do_---- 17. 2 16. 0 28.6 Source: Bras, I. D. J., Tidings, J. (14). TABLE 16.-Percentage of British males who reported inhaling a lot or fair amount of cigar smoke by curren.t and previous tobacco usage and type of tobacco previously smoked (1968) Type of tobacco smoked Number of Percentage - individuals Type inhaled inhaled Current usage Prev ous usage Cigarettes only.-_ _ _ _ . _ Cigarettes only- -- - - - 2, 586 Cigarette.- _ _ _ 77. 7 Cigars only-. _. _ _ _ _ _ __ Nonsmoker- - - - _ - __ _ 306 Cigars..---- 18. 0 Cigars only.. - _____.___ Cigarett,es only _____._ 321 -~_~-do--_-__- 30. 0 Source: Todd, 0. F. (94). 188 TABLE 17.-Extent of reported inhalation of ciga.r smoke by British male cigar smokers who were es-cigarette smokers in 1968, analyzed by extent of reported inhalation of cigarette smoke when previously smoking cigarettes Extent of inhaling cigars Extent of inhaling cigarettes Inhale a lot Inhale a little or fair amount or not at all PerCell Pl?rCent Inhalealotorfairamount-_---- ______ -_-__-_--_- 44. 0 5. 0 InhalealittleornotatalI~-._-_-- ____. -_-__-__-_- 56. 0 95. 0 Source: Todd, G. F. (97). Specific Causes of Mortality Cancer Several prospective epidemiological studies have shown a signifi- cantly higher overall cancer mortality among pipe and cigar smokers compared to the cancer mortaljty of nonsmokers (table 18). Pipe and cigar smokers have much higher rates of cancer at certain sites than at others. The upper airway and upper digestive tracts appear to be the most likely target organs. The relationship of pipe and cigar smoking to the development of specific cancers is detailed in the following sections. TABLE 18.-Mortality ratios for totd cancer deaths in cigar and pipe smokers. A summary of prospective epidemiological studies Author, reference Type of smoking Nonsmoker Cigar only Pipe only Total pipe and cigar Cirp.~tte Hammond and Horn (40)---- 1. 00 1. 34 1.44 ---- ---- 1. 97 Best (9)-- _____ - _______-_-_ 1. 00 1. 13 1. 38 _ _ _ - _ _ _ _ 2. 06 Hammond (38)---- _ _ _ _ ___ _ _ 1.00 ------- ------- 1. 21 1. 76 Kahn (60)_-----_._________ 1. 00 1. 22 1. 25 1. 25 2. 21 189 Cancer of the Lip Approximately 1,500 new cases of cancer of the lip are reported each year. Because of the possibility of early detection and surgical accessibility of cancers in this area, there are less than 200 deaths from cancer of the lip each year in the United States. Some of the earliest scientific investigations exploring the association between tobacco use and disease examined the smoking patterns of individuals with cancer of the lip. Broders (13) in 1920 examined the smoking habits of patients in a retrospective study of 526 cases of epithelioma of the lip and 5~ controls. Of the cancer cases, 59 percent smoked pipes, whereas this was true for only 28 percent of the controls. No association was found between cigar or cigarette smoking and cancer of the lip. In a restrospective study of 439 clinic patients with cancer of the lip and 300 controls conducted in Sweden, Ebenius (32) reported 8 significant association bettveen pipe smoking and cancer of the lip. A total of 61.8 percent of the lip cancer cases smoked pipes, while only 22.9 percent of the controls smoked pipes. NO association ITas found between the use of cigarettes, cigars, or chewing tobacco and cancer of the lip. In other retrospective studies, Levin, et al. (60) reviewed a series of 143 cases of cancer of the lip, and Sadowsky, et al. (77) reviewed 5'71 cases of cancer of the lip. 1.n both studies, a strong association ras found between pipe smoking and cancer of the lip. No significant association was found between the use of tobacco in other forms and cancer at this site. In a study of environmental factors in cancer of the upper alimen- tary tract, Wynder, et al. (11'S) found an association between pipe smoking, cigarette smoking, and cancer of the lip. There were only 15 cases of cancer of the lip in this study. Staszewski (87) examined the smoking habits of 394 men with carcinoma or precancerous lesions of the lips. An association lvas found between the smoking of pipes and cigars and cancer of the lip* but this was only of doubtful significance. A significant association was found between the use of cigarettes and cancer of the lip. Keller (51) conducted a study of lip cancers in which he considered a number of factors including histologic types, survival, race, occupa- tions, habits, and associnted diseases. A total of 304 patients with primary basal cell or squamous cell carcinoma of the lip and :W controls from the same hospital matched for age and race were con- sidered in this series. A significant association was found between smoking in all forms and combinations and carcinoma of the lip. lt \f'as also found that increasing age and outdoor occupations with exposure to the sun were equally significant factors in the etiology of lip cancer. 190 In summary, it appears that there are several factors involved in the etiology of cancer of the lip. -4mong the various forms of tobacco use, pipe smoking either alone or in combinat,ion with other forms of smoking seems to be a cause of cancer of the lip. Table 19 summarizes the results of these retrospective studies. Oral Cancer The lips, oral cavity, and pharynx are the first tissues exposed to tobacco smoke drawn in through the mouth. Variations in inhalation during the smoking of various tobacco products result in different pat- terns of distribution of smoke throughout, t.he respiratory tree. How- eve,r, the oral cavity and adjacent tissues are the sites most. consistently exposed to tobacco smoke. For this reason, differences in inhalation should result in less variation in exposure to tobacco smoke for these sites than for t,he lower t,rachea and the lung. The, inherent carcinogen- icity of pipe, cigar, and cigarette smoke is most reliably compared at t.hose tissue sites where dosage and exposure to tobacco smoke are most nearly equal. Data from the epidemiological studies suggest that little difference exists between the smoking of cigarett'es, pipes, or cigars and the risk of developing oral cancer. Hammond and Horn (JO) examined the association between smok- ing in various forms and cancer of the combined sites of lip, mouth, pharynx, larynx, and esophagus. The mortality ra.tios were 5.00 for cigar smokers, 3.50 for pipe smokers? and 5.06 for cigarette smokers compared to nonsmokers. All the deaths from cancer of the lip, oral cav- ity, and pharynx reported by Doll and Hill (Z'(3) occurred in smokers. The death rates from cancer at these sites were 0.04 per 1,000 for pipe and cigar smokers, 0.10 per 1,000 for mixed smokers? and 0.05 per 1,000 for cigarette smokers. A fairly detailed analysis of oral cancer was pre- sented by Kahn (50) who differentiat.ed between cancer of the oral cavity and cancer of the pharynx. The mortality ratios for oral cancers were 1.00 for those who never smoked, 3.89 for all pipe and cigar smoke.rs, and 4.09 for cigarette smokers. A further breakdown of the pipe and cigar smokers demonstrated a mortality rat.io of 4.11 for cigar smokers, 3.12 for pipe smokers, and 4.20 for smokers of pipes and cigars. For cancer of the pharynx, the mortality ratios were 1.00 for those who never smoked, 3.06 for all pipe and cigar smokers, and 12.5 for cigarette smokers. No deaths occurred among those who smoked only ciga.rs. The mortality ratio was 1.98 for pipe smokers and 7.76 for smokers of pipes and cigars. Hammond (58) combined cancers of the lip, oral cavity, and pharynx. The pipe and cigar smokers had a mortality ratio of 4.94 and the cigarette smokers a mortality ratio of 9.90 compared to nonsmokers. 191 TABLE lg.---Relative risk of lip cancer for men, comparing cigar, pipe, and cigarette smokers with nonsmokers. A summary qf retrospective studies Arlrllor rt~f?rt.rlrt~ Helatiw risk ratio and percentage of ctlses and cmtrols by type of smoking Nulr,ber -----~- ~.---.-------------_~- ----- ------__ Nonsmoker Cigar only Pipe only Total pipe Cigarette Mired and cigar only -- __ .-~ - Broders (15) : Relative risk ______ --_-.- Cases-m.mm--_-m. __-.--. ~_- 537 Percent cases-_-------m- Controlsmm ~--_--~..---_-~~-~- 600 Percent controls----_-_.- Relative risk-m------_.--_ Percent cases-----.-m--- Percent controls-.._-__ Levin, et al. (CO): f--o-n. YU.?Ci)_ ---__--~-~--_-_~---__ 146 Controls --__-.----___~----_ 554 Relative risk_--_m-m--_-_ Percent cases-----m__--- Percent controls_--._---- Relative risk ____ -_--__-_ Percent cafes- _ _ _ _ . _ - _ - - Percent controls--. - ___ Wynder,' et al. (Ifs) : Cases-.__----_-___-_-~--~--~ 14 Controls--_-__---_-_________ 115 Relative risk--__--_--_-- Percent cases- _ -. _ _____ - Percent controls. _______ Staszewski (87) : Cases-____~__-._-_.__-----~~ 394 Controls __--_. _. _ _ -. --_-_ _ --_ 912 Keller: (61) : Relativerisk-_-_---- ____ Percent cases--_--..------ Percent controls_ _ _ _ _ _ _ - Cases-.-m--- _____ -__-_----_ 301 CoIltrols--~-- .__. ~_-- _____ --_ 265 Relativerisk-_-_--..-.__ Percent cases- ___. -_-___ Percentcontrols-__----- 1. 0 0. 8 4. 3 - _ -. _ _ _ _ _ 0 .____-__ - 7 19 41 -__---___ 1 _____ -__ 4 16 6 -____-_-- 26 _ _ _ _ _ _ _ _ _ 1. 0 6' 7 4. 1 0.5 -- _.___ ^. _- _-__ 49 41 4 65 12 13 10 ----__- -~- -___ -_ 1. 0 1. 9 15 27 22 20 1. 0 1. 1 8 2 13 3 0 8 0 7' 24 9 1.0 - ________ 5 _--_- ____ 13 _ _ - _ _ _ __ _ 1. 0 1. 4 7 2 17 4 4. 3 2. 6 18 6 7 4 1.8 ___---___ 29 .______ ~_ 16 _ _ _ _ _ _ _ _ _ 2. 1 12 - _ . _ - - _ 11 4. 0 6 1 3 0 I. 1 ___-_ -___ 45 ___-__. -_ 46 _____ -_-_ 1. 4 0. 4 44 22 53 19 1. 0 2. 2 36 29 36 13 2.4 -_-_--_-- 73 ______--_ 61 _________ 2. 6 60 6 53 0 These studies are summarized in table 20. They demonstrate that smokers experience a large. and significant risk of developing cancer of the oral cavity compared to nonsmokers. This risk seems to be about the same for all smokers whethe.r an individual uses a pipe., cigar, or rigare&. A number of retrospective studies have examined the relat,ionship betwwn smoking in various forms and cancer of t.he oral cavity. The results of these studies are presented in table 21. Some of the variations in relative risk of developing oral cancer observed in the retrospect,ire studies is probably due to the lack of a uniform definition of oral cancer by anatomical site and the variolls means used in selecting and defin- ing cases and controls. It appears, however, t,hat a significant risk of developing oral cancer exists for smokers compared to nonsmokers and t.his risk is similar for smokers of pipes, cigars, and cigarettes. Several epidemiologic.al investigations have demonst,rated an asso- ciation between the combined use of alcohol and tobacco and the development of oral cancet . A few of these studies ($2. 62, 6.7. 10.9) ront.ain data on pipe and cigar smokers. Heavy smoking and heavy drinking are associated with higher rates of oral cancer than are seen with either habit alone. TABLE 20.-Mortality ratios for oral cancer in cigar and pipe smokers. A summary of prospective epidemiological studies Author, reference smoking type ----__ -- ---__- Non- Ci ar Pi e SlllOker d P Total pipe Cigarette Mixed 0 Y on Y and cigar OdY Hammond and Horn'(@) _ 1. 00 5. 00 3.50 --__---- 5.06 -- .--__- Doll and Hill 2 (16, 97) - - . 0.00 -__--_-- - _-.- - 0. 80 1. 00 2. 00 Hammond (98)---_--_--- 1. 00 - _ _. _ - - - _ - -. . _ 4. 94 39.90 __-.--- - Kahn (60): Oral 4.. ___---_--__-- 1. 00 4. 11 3. 12 3. 89 4.09 --__--_- Pharynx----_---_--_ 1. 00 _ _ _ - - _ _ - 1. 98 3. 06 12.54 -___--_- * Combines data for oral, larynx, and esophagus. 2 Ratios: relative to cigarette smokers. 3 Mortality ratios for 45 to 64 ages only are presented. ' Excludes pharynx. Cancer of the Larynx The larynx is situated at. the upper end of the trachea. Because of its proximity to t,he oral cavity, the larynx probably has a similar exposure to smoke dra#wn through the mouth as the buccal cavity and pharynx. Tobacco smoke that is not inhaled may still reach as far as the larynx and upl)er trachea. Pipe and cigar smokers develop cancer of the larynx at rates comparable to those of cigarette smokers. These 193 P TAJILK 21.--Relative risk of oral cancer for men, comparing cigar, pipe, and cigarette smokers uith nonsmokers. A summary of retrospective studies Author, rekwncr Relative risk ratio and percentsge of cases and controls by type of smoking Number ---_----------__----- Nonsmoker Cigar only Pipe only Total pipe Cigarette and cigar OdY Mixed dadowsky, et ai. (iii: CaseS------_._______--~----- Controls-~_._---------- __.___ Schwartz, et al. (83) : Cases--_-_._-- -------__~-- Controls-----._~_~.--.- __.._ Wynder, et al. (209): Cases--_----_-- _________.___ Controls~~....----_- _______ -_ 1, 136 615 332 608 543 207 Relative risk--- - - _ _ _. _ _ _. Percent cases- _ _ _ __ _. _ _ __ Percent controls-- - _ _ _ _ _ __ iieiative risk-~._~__--_--- Percent cases-_--------_- Percent controls-. - _ _ . _ _ _ _ Relative risk----~-__-_--_ Percent cases-----_--_--- Percent controls-- - - _ _. _ _ 1.0 --____--- -_-_--~- 7. 0 10 -_---___- --._._.. 55 38 _.__~_.__ ____--._ 30 1. u 8 13 ___ ___ 1. 0 16 23 Relative risk _____________ 1. 0 Percent cases_- _____ -_--_ 3 Percent controls-- ________ 10 Relative risk_--- - _ _ _ _ _ _ _ _ 1. 0 Percent cases----___----- 23 Percent controls-----__--- 26 2. u 4.4 --_---___ 4 18 --_. --___ 3 7 _____~_._ 1.6 ___---___ __---- 3 _____ -_-_ 77 3 -- _______ 3. 6 6. 1 - ________ 20 11 ~-_-- ___- 13 6 ___-_-___ 1.7 . 9 -_-_-____ 13 12 -----_--_ 9 16 _____---_ 1. 4 2. 1 42 28 53 23 1.5 - -_____ -- 63 _______ -_ 58 __ -_--._ 3. 0 3. 3 57 8 63 8 1. 2 1. 4 37 16 36 13 k Staszewski (87): Cases __._ ._____ -__-~--___-- Controls- _.______ -__--_~--___ Martinez (69) : 178 220 1,400 713 383 912 408 408 170 510 346 346 Relative risk_---~_.-~---. Percent cases--_----~---- Percent controls_-- _ _ ___ _ _ Relative risk-_--~---_---- Percent cases---.--- .____ Percent controls--_-_----_ Relative risk----.--_~---- Percent cases_- ____ -___-- Percent controls----_-- .-_ Relative risk_-- ._____ ---_ Percent cases- - ___-___-__ Percent controls---- _ _ ____ Relative risk---~--~_-_--_ Percent cases---U------_- Percent controls--- _ - _ _ - -_ Relative risk_--- ____ -_~-_ Percent cases- _ - _______ -- Percent controls__ _ _ _ _ - - - _ 1. 0 6. 0 4 33 16 22 1.0 _------_ 21 _--_-_-_ 39 ---_-_-_ 1.0 ~_.__.~. 6 ---___-_ 17 ---___-- 1. 0 3. 1 5 7 11 6 1. 0 1. 7 8 10 14 10 1. 0 2. 0 12 10 22 9 3.6 -~ -_____ 10 _---_--_ 5 _---_- _____- _____- 3. 8 4 3 1. 3 1 2 2. 8 3. 5 13 11 2. 2 10 13 ___-___- .___-_-- 15 __--_--_ 1 ___----- 4.0 ___-_ -._-- 45 --___-_-. 45 ~_.._____ 2. 2 2. 9 59 11 50 7 3. 6 -_~-___-- 72 _--_-____ 61 __-__--__ 3.4 ___-- ---_ 69 -___----_ 56 ~-___--_. 1. 5 2. 3 39 34 44 25 1. 7 2. 5 34 34 36 25 ' This study combines data for oral CmCeI and mncer of the esophagus. rates are several times the rates of nonsmokers. The similarity of the mortality ratios of cancer of the laqwx for smoking in various forms suppcsts that, the carcinogenic potentials of the smoke from cigars, pipes. and cigarettes are quite alike at this site. Sewral of the prospective epidemiological studies include data on deaths from cancer of the larynx for pipe and cigar smokers as \T-ell as for cigarette snlokers. Hammond and Horn (.&I) combined data for cancer of the larynx with cancer of the esophagus and oral cavity. The mortalit,y ratios compared to nonsmokers were 5.00 for cigu smokers, 3.50 for pipe smokers, and 5.06 for cigarette smokers. There were no deaths from carcinoma of larynx among nonsmokers in the study of British physici;ms by Doll and Hill (%%) ; however, the de&h rate for cancer of the larynx among pipe and cigar smokers was 0.10 per 1,000 while the death rate for cigarette smokers was 0.05 pe1 1,000. Kahn (50) reported mortality ratios for c.ancer of the larynx of 10.33 for cigar smokers, 9.44 for pipe and cigar smokers, 7.28 for all pipe and cigar categories combined, and 9.95 for cigarette smokers. No deaths from cancer of t.he lar,ynx occurred in pipe smokers. Hammond (.?a) reported a mortality ratio of 3.37 for all pipe and cigar smokers and a mortality rat.io of 6.09 for cigarette smokers in the age category 45 to 64. These studies are, summarized in table 22. Several retrospective studies have examined the smoking habits of patients with cancer of the larynx and appropriately matched controls. The small number of pipe and cigar smokers in each study results in relative risk ratios that are quite unstable; however, it appears that pipe and cigar smokers experience a risk of developing cancer of the larynx that is similar to the risk observed among cigarette smokers (table 18). TABLE 22.-Mortality ratios,for cancer qf the larynx in cigar and pipe smokers. A summary qj' prospective epidemiological studies Author. reference Smoking type Non- Cigar only Pipe only Total pipe Cifrpe Mixed smoker and cigar Hammond and Horn 1 (~o)--------~------~-~ 1. 00 5. 00 3.50 -------- 5. of3 . . . . ..~. Doll and Hill * 126, 27) ~. 0.00 -- ----- ~----- 2. 00 1. 00 0. 60 Hammond (381.----... 1.00 ~._~~~_~ ~_~~~~ 3. 37 3 6.09 ~.~~~~.~ Kahn iSO)----------..-- 1. 00 10. 33 ~-~~~~ 7.28 9.95 ~.....~. 1 Combines data for oral, larynx. and esop~gus. 1 Ratios: relative to cigaretle smokers. 3 Only mortality ratios for ages 4.5 to 64 BTG presented !96 Wynder, et al. (108, 113) distinguished between intrinsic and ex- trinsic larynx cancers. For smokers the relative risk of developing cancer of the intrinsic larynx was similar to the relative risk of lung cancer whereas the relative risk of developing extrinsic larynx cancer was more like the relative risk of cancer of the upper digestive tract. Histologic changes of the larynx in relation to smoking in various forms were described by Auerbach, et al. (5). Microscopic sections of the larynx from 042 subjects were examined for the presence of atypical nuclei and proliferation of cell rows. Sections we.re taken from four separate areas of the larynx in each CXCX. ,imong t,hose who smoked cigars and pipes but not cigarettes. only 1 percent, had no atypical c.ells and more than 75 percent of t.he subjects had lesions wit,h 50 to 69 percent, atypical cells. Four of the cigar and pipe smokers had carcinoma in sit.u and in one of t.hese four cases early invasion was seen in three of the sections. Of those n-ho never smoked re,gu- larly, 75 percent had no at,vpical cells. The cigar and pipe smokers had a similsr percentage of cells with at.ypic.al nuclei as cigarette smokers \r-ho smoked one to t.wo packs per day. With respect to the prolifera- tion of cell rows in the basal layer of the true vocal cord, the least proportion of cases with eight or more cell rows was found in men who never smoked, and the greatest proportion was found in heavy cigarette smokers. Pipe and cigar smokers had a distribution of cell POWS that, was comparable to that of cigarette smokers who consumed about a pack a day. Several ret.rospective studies have, reported an associat,ion between the combined use of tobacco and alcohol and cancer of the la.rynx. A study by Wynder, et al. (108) included some informat.ion on pipe and cigar smoking in relation to drinking habits and the development, of cancer of t,he larynx, but because of t.he limited number of pipe and cigar smoking subjects this relationship could not be adequately determined. Cancer of the Esophagus The esophagus is not directly exposed to tobacco smoke drawn into the mout,h; however, the esophagus does have contact with t.hat portion of tobacco smoke that is condensed on the mucous membranes of the mout.h and pharynx and then swallowed. The esophagus is also ex- posed to a portion of tobacco smoke that, is deposited in t.he mucus cleared from t.he lung by the ciliav mechanism or by coughing. Varia- tions in inhalation of a tobacco p&duct may not appreciably alter the exposure the esophagus receives from smoke dissolved in mucus and saliva. This suggest.ion receives support from the prospective and rebrospect.ive epidemiological studies which demonstrate similar mor- tality rates for cancer of the esophagus in smoke,rs of cigars, pipes, and cigarettes. 197 Relative risk ratio and prrcentwe of CBS~S and controls by type of smoking --~.-~__-- Nonsmoker (`ignr only Pipe only Total pipe and cigar cigarettr OIllY Mixed TABLE %.-Relative risk qf can,cer qf the larynx .for men, comparing cigar, pipe, and cigarette smokers with nonsmokers. A summary qf retrospective studies Author. rrlwrnc, ___-.. Number Relativerisk--- -----_-- Percent casts- 1. 0 0 1.1 _.___._~_ 14 0 ? -------__ 24 10 11 __------- Percent controb-_m_--__- 2.3 -_-- _____ so -----____ 59 ~.~__.___ Sadowsky, et al. (77) : Cases---- ~~~----___--~.~--- 273 Controls _.__ ~~-~---._-_-_~_~- 615 Relative risk----_-~ -~_-_ Percent cases- _ _ _ _ _ _ - - Percent controls-----_.-. 1. 0 2. 2 2.3 ______- -- 4 2 5 _ - _ _ _ _ _ - _ 13 3 7 _ _ _ _ _ _ _ _ _ 3. 7 4. 1 60 29 53 23 Relative risk---_-_--m_-- Percent cases--- ____ --._ Percent controls__-__-_-- 1. 0 15. 5 27. 7 11. 1 .5 8 5 1 11 10 4 2 24.6 _____ -__- 86 ___._ -- ._ 74 _ _ - - - _ _ _ - Wynder, et al. (ZfS): Casese--m------ ____ -._~--- 60 Controls---_.~_-___-_--.~ -._ 271 Relative risk_---_--.._-_- Percent cases----_---__- Percent controls__--___-_ 1. 0 9. 7 4.5 _-_----__ 5 17 15 --_____ -_ 24 9 16 _______ -_ 6. 3 6. 3 47 17 36 13 Wynder, et al. (116) : Relative risk- _ _ - - _ _ - _ _ _ Cases_----~-~_---_~--______ 142 Percent cases- _ _ - _______ Controls-..~~ ._~--__-~-._~._. 220 Percent controls-------_- 1. 0 14. 5 16.0 ___._ -___ 1 20 1 _-__ --___ 16 22 1 _--~-__-_ 22. 0 16. 0 62 16 45 16 Pernu (75) : Relative risk__------_--_ 1.0 --. --._-_ 4.5 -_--___-- 8. 7 3. 2 Cases.~~~------___-_-----_~~ 546 Percent cases _______. --_ 7 ___..__ ~_ 4 - _______ - 78 4 Controls------___- __________ - 713 Percent controls--------- 39 ___- ___._ 5 _ r _ _ . . _. 50 7 Staszewski (87) : Relative risk-.---..---- 1.0 -- _-_-___ ___---_ 5. 9 50.2 ___-_-___ Cases-..._~-~-._~------_____ 207 Percent cases _________ -_ .5 --_-----_ ___---- 2 88 -----__ -_ Controls_-----.._--- _._._.___ 912 Percent controls--------_ 17 .__-_-___ _______ 11 61 ___-----_ Svoboda (!/O) : Relative risk_------ 1.0 --_---_-_ 2.6 ___---___ 10.0 -________ Cases_._._____-___~-----~~_- 205 Percent cases------ ___._ 3 .__---___ 3 _ _ _ _ _ _ - - - 95 - - - - _ _ _ _ _ Controls--- ____.__ --~~~ . . . .._ 320 Percent controls__-m--_-- 22 _____ -___ 7 -- _______ 71 -- _______ Stell (88) : Relative risk___----- _... 1.0 -- _______ --__--_ 1. 3 2.4 -_-- _____ Cases--. .~~~---._____----~_ 190 Percent cases..-------_-_ 11 .__-- ____ ___--__ 8 79 --~-_-_-- Controlsmm_- -_~.--- _____._. - 190 Percent controls ________ - 17 --_._-.-- _____ -- 10 50 __-----~- In t,he prospective epidemiological studies, cigar, pipe, and cigarette smokers all had similar mortality ratios from cancer of the esophagus. Hammond and Horn (40) combined the categories of carcinoma of the e.sophagus, larynx, pharynx, oral cavity, and lip and described mortality ratios of 5.00 for cigar smokers, 3.50 for pipe smokers, and 5.06 for cigarette smokers. Doll and Hill ($6) reported an esophageal ancer mortality ratio of 2.0 for pipe and cigar smokers, 4.8 for mixed smokers, and 1.5 for cigarette smokers. Kahn (60) reported the fol- lowing mortality ratios for smoking in various forms compared to non- smokers: cigar only, 5.33: pipe only, 1.99; pipe and cigar, 4.17; all pipes and cigars combined, 4.05; a.nd cigarettes only, 6.17. The results of these prospective st.udies are summarized in table 24. Several retrospective inrestigat,ions have also examined the associa- tion between smoking in various forms and cancer of the esophagus. These studies have been summarized in table 25. The evidence sug- gests that cigar, pipe, and cigarette smokers develop cancer of the esophagus at rates substantially higher than those Seen in nonsmokers, and that lit.tle difference exists between these rates observed in smokers of pipes and cigars and cigarettes. Histologic c.hanges in the esophagus in relation to smoking in vari- ous forms were investigated by Auerbach, et al. (`r), who looked for atypical nuclei. disintegrating nuclei? hyperplasia, and hyperactive esophageal glands. A total of 12.598 sections were made from tissues obtained from 1,268 subjects. For each of the parameters investigated, pipe and cigar smokers tlenlonstrated significantly more abnormal histologic changes than nonsmokers J however, these changes were not as severe or as frequent as those seen in cigarette smokers. Several retrospective studies conducted in the United States and other countries have examined t.he synergistic roles of tobacco use and heavy alcohol intake on the development of cancer of the esophagus. Four of these invest.igations contain data on pipe and cigar smoking (12. 6,". @. 107). It appears that smoking in any form in combination with heavy drinking results in especially high rates of cancer of the esophagus. TABLE 24.--,&fortali.ty ratios jbr cancer of the esophagus in, cigar and pipe smokers. A summa y qf prospective epidemiological studies - Smoking type Author, reference NOW Cigar smoker only ------____-- Pi e Total 3 Cigarette 0 Y pipe and CdY Mixed cigar Hammond and Horn I(@) 1. 00 .i. 00 3.50 -----_-- 5.06 ----_..r Doll and Hill (86, 87).--- 1.00 _--~---- _..~_. 2. 00 1. 50 4. 80 Hammond (S8).------_-- 1.00 2 _.--._-. _---_- 3. 97 4. 17 --..---. Kahn (60)-~~--..-..~-.~ 1. 00 5. 33 1. 99 4. 05 6. 17 ._- _..._ 1 Combines data for oral. larynx, and esophaqu 2 Mortality ratio for ages 45 to 64. 200